HMB β-Hydroxy β-methylbutyric acid whats the deal?

[ss4vegeta1]

It has been established that BCAAs are not necessary when there is ample amino acids coming from the diet. But i heard Layne mention something in regards to this. Is HMB really worth investing? What does the science say. Thanks in advance.

[AphtaLyfe]

Is HMB really worth investing? What does the science say. Thanks in advance.

The only populations that HMB has been definitively shown to benefit are those with conditions that result in muscle wasting or excessive catabolic states. In healthy experienced athletes/weight lifters the studies have been more conflicted.

[littlebones6]

Or teh newbs. After 8-12 weeks of training experience it's effect starts to wear off quickly.

[KevJr88]

It has been established that BCAAs are not necessary when there is ample amino acids coming from the diet.

I would actually argue this point. Not necessary, right. If you eat a serving of meat a day no supplemental protein is "necessary." Not useful? After having been shown in study, after study, after study to increase muscle protein synthesis? C'mon.

[shobhit1978]

β-Hydroxy-β-methylbutyrate (HMβ) supplementation stimulates skeletal muscle hypertrophy in rats via the mTOR pathway
Gustavo D Pimentel,corresponding author1,2 José C Rosa,1 Fábio S Lira,1 Nelo E Zanchi,3 Eduardo R Ropelle,2,4 Lila M Oyama,1 Cláudia M Oller do Nascimento,1 Marco Túlio de Mello,5 Sergio Tufik,5 and Ronaldo VT Santos6
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Abstract

β-Hydroxy-β-methylbutyrate (HMβ) supplementation is used to treat cancer, sepsis and exercise-induced muscle damage. However, its effects on animal and human health and the consequences of this treatment in other tissues (e.g., fat and liver) have not been examined. The purpose of this study was to evaluate the effects of HMβ supplementation on skeletal muscle hypertrophy and the expression of proteins involved in insulin signalling. Rats were treated with HMβ (320 mg/kg body weight) or saline for one month. The skeletal muscle hypertrophy and insulin signalling were evaluated by western blotting, and hormonal concentrations were evaluated using ELISAs. HMβ supplementation induced muscle hypertrophy in the extensor digitorum longus (EDL) and soleus muscles and increased serum insulin levels, the expression of the mammalian target of rapamycin (mTOR) and phosphorylation of p70S6K in the EDL muscle. Expression of the insulin receptor was increased only in liver. Thus, our results suggest that HMβ supplementation can be used to increase muscle mass without adverse health effects.
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Introduction

The amino acid leucine has been shown to stimulate skeletal muscle protein synthesis and attenuate muscle proteolysis. Some of these benefits have been attributed to the conversion of leucine to its metabolite β-hydroxy-β-methylbutyrate (HMβ) [1-4], which has been shown to be anti-catabolic and effective at attenuating muscle atrophy during exercise stress [2,5,6] and in models of cancer [4,7], congestive heart failure, sepsis, and HIV [8,9]. According to a review published by Nelo et al. [10], the dose of HMβ supplementation used in the majority of the previous studies to achieve these effects was 3 g/day of HMβ; use of this dose is based on evidence that it produces better results than 1.5 g/day.

HMβ is produced by the transamination of α-ketoisocaproate (KIC), which is metabolised to isovaleryl-CoA by the enzyme KIC dioxygenase. The cytosolic dioxygenase enzyme differs from the mitochondrial KIC dehydrogenase enzyme in several ways. KIC dioxygenase produces free HMβ in the cytosol, whereas the dehydrogenase enzyme produces the CoA derivative of isovaleric acid in the mitochondria [11,12]. Quantitatively, it is estimated that approximately 5% of all L-leucine oxidised in the human body is converted to HMβ. Therefore, a subject weighing 70 kg produces approximately 0.2 - 0.4 g HMβ/day, depending on the content of leucine in the diet. Because leucine, like all essential amino acids, is not synthesised in the human body, HMβ is produced from dietary protein [13].

The results of trials evaluating the effect of HMβ supplementation on reversing cachexia associated with rheumatoid arthritis [14], HIV [8], and muscle damage [15,16] are performed merely with biochemical markers. Additionally, most of the available studies concerning the effects of HMβ are related to effects on skeletal muscle, with an absence of relevant information concerning consequences in other peripheral tissues (e.g., adipose tissue and liver).

Recently, Holecek et al. [17] demonstrated increases in protein synthesis in the liver upon HMβ supplementation. However, the authors did not describe the mechanisms involved in this increase. Moreover, descriptions of the effects of HMβ alone (i.e., in normal situations without exercise or excess catabolism) are scarce.

Taking this into consideration, we aimed to examine the effect of HMβ supplementation on skeletal muscle hypertrophy in healthy and sedentary rats. The expression of the mammalian target of rapamycin (mTOR) and other proteins involved in insulin signalling were investigated to better understand HMβ-stimulated skeletal muscle hypertrophy.

[shobhit1978]

Methods
Animals

The Experimental Research Committee of the Federal University of São Paulo approved all procedures for the care of the animals used in this study. A total of 14 male Wistar rats ranging in age from 8-9 wks and weighing between 200 and 250 g were used. They were housed four per cage, with a chow diet (NUVILAB) and water ad libitum, in an animal room with a 12 h light-dark cycle at 22 ± 1°C and 60 ± 5% humidity. The experiments were carried out after an acclimation period of one week.
HMβ supplementation

Supplementation was carried out by intragastric administration (gavage) of 320 mg/kg body weight of HMβ (Dymatize Enterprises Inc, Dallas, TX, USA) diluted in 1.0 ml of water. HMβ was given daily at the same time (during the light period) for one month (at 3-4 months of age). This dose of supplementation was previously described by our group [4]. The control group was not submitted to the supplementation protocol and was treated with water by gavage.
Blood glucose and lipidic profile measurements

Approximately 15-18 hours after HMβ oral gavage and after a 12 hour fast, the animals were euthanised by decapitation, blood was collected, and serum samples were collected after allowing the blood to clot on ice. Serum was stored frozen at -80°C for analysis. Labtest® kits were used to assess fasting blood glucose, total cholesterol, high-density lipoprotein (HDL-c) and triacylglycerol (TG) levels. The samples were analysed using an enzymatic method. LDL-c and VLDL-c were calculated according to the Friedwald equation ((LDL-c = total cholesterol-(HDL-c)-(TG/5) and (VLDL = TG/5)) [18], and LDL-c subclass, which is a good predictive factor for oxidised-LDL-c, was calculated using the equation LDL-c = TG/HDL-c [19].
Serum hormone levels

Serum fasting insulin, testosterone and corticosterone levels were quantified using enzyme-linked immunosorbent assay (ELISA). The insulin ELISA kit was obtained from Millipore Corp. (Bedford, MA, USA), and the testosterone and corticosterone kits were from Assay Designs, Inc. (Ann Arbor, MI, USA).
Hepatic content of total lipids

The liver lipids were extracted according to the method of Folch [20].
Protein analysis by western blotting

After euthanasia, the extensor digitorum longus muscle (EDL), retroperitoneal adipose tissue (RPAT), and liver tissues were rapidly removed and homogenised in 1.5 ml extraction buffer (100 mM Trizma, 1% SDS, 100 mM sodium pyrophosphate, 100 mM sodium fluoride, 10 mM EDTA and 10 mM sodium vanadate) and boiled for 10 min. The extracts were then centrifuged at 12,000 rpm at 4°C for 40 min to remove insoluble material. Supernatant protein concentration was determined using the Bradford dye method with a Bio-Rad reagent (Bio-Rad Laboratories, Hercules, CA, USA). The proteins were added to Laemmli sample buffer containing dithiothreitol and boiled for 5 min before loading onto 10% SDS-PAGE gels in a Bio-Rad miniature slab gel apparatus. Electrotransfer of proteins from the gel to nitrocellulose was performed for ~1 h at 15 V (constant) in a Bio-Rad semi-dry transfer apparatus. Nonspecific protein binding to the nitrocellulose was reduced by preincubation for 2 h at 22°C in blocking buffer (5% nonfat dry milk, 10 mM Tris, 150 mM NaCl and 0.02% Tween 20). The nitrocellulose membranes were separately incubated overnight at 4°C with antibodies against phospho-p70S6K, phospho-Akt, mTOR, GLUT-4, and Akt/PKB (Cell Signaling Technology® (Danvers, MA, USA)) or AMPK, p70S6K, IR (insulin receptor) and alpha-tubulin antibodies, which were obtained from Santa Cruz Biotechnology (Santa Cruz, CA, USA), diluted in blocking buffer added with 1% bovine serum album (BSA) and then washed for 30 min in blocking buffer without BSA. The blots were subsequently incubated with peroxidase-conjugated secondary antibody for 1 h.

For evaluation of protein loading, membranes were stripped and reblotted with an anti-alpha-tubulin antibody. Specific bands were detected by chemiluminescence, and visualisation/capture was performed by exposure of the membranes to RX films. Band intensities were quantified by optical densitometry of developed autoradiographs (Scion Image software-Scion Corporation, Frederick, Md., USA).
Statistical analysis

The statistical analysis was performed using the GraphPad Prism statistics software package version 5.0 for Windows (GraphPad Software, San Diego, CA, USA). The data are expressed as the means ± SEM. Implementation of the Kolmogorov-Smirnov test revealed that the results of experiments were distributed normally. The data were analysed using Student's t-test for comparison between two groups. A value of P < 0.05 was considered statistically significant.

[shobhit1978]

Discussion

The present study sought to evaluate the impact of HMβ supplementation on the expression of proteins involved in skeletal muscle hypertrophy in healthy and sedentary rats and proteins involved in insulin signalling. Our results show that HMβ supplementation increased mTOR expression and phosphorylation of p70S6K in the EDL muscle while increasing fasting insulin levels and testosterone/corticosterone ratios and decreasing fasting glucose and corticosterone levels in the serum.

As previously described, HMβ is a widely studied metabolite of leucine. Several reports have shown that branched-chain amino acids (BCAA), isolated leucine and HMβ can stimulate skeletal muscle protein synthesis and activate the mTOR pathway in skeletal muscle [9,21] as well as in primary hepatocytes [22].

In the present study, we observed that, relative to the control group, the supplemented group demonstrated an increase in mTOR protein levels and activation of p70S6K, which are linked to increased skeletal muscle mass in the EDL muscle. Our findings are supported by a recent study by Lang's group [23] showing that gastrocnemius mass and protein synthesis were robustly decreased in mTOR heterozygous mice compared to wild type mice. Based on this information, we conclude that not only the activity but also the level of mTOR is an important regulator of skeletal muscle mass.

Contrary to what was observed in the present study, Ostaszewski et al. [24] and Holecek et al. [17] did not observe increased protein synthesis in the EDL and soleus muscles after HMβ supplementation but measured consistently decreased protein degradation, as estimated by the net release of tyrosine from incubated muscles.

In the present study, we analysed the expression of AMPK, which is known to be an important regulator of muscle protein synthesis [25,26], but we found no differences between the groups.

In the present study, we found no alterations in the Akt/PKB pathway in the EDL muscle. Thus, we suggest that increased skeletal muscle protein mass by HMβ supplementation was induced directly via increased mTOR expression and activation of p70S6K and not via phosphorylation of Akt/PKB. However, as previously shown in several studies, constitutive activation of Akt/PKB is capable of inducing skeletal muscle hypertrophy [27-29], although we did not observe this effect in our study. Moreover, as the molecular analyses were performed 15-18 hours after HMβ oral gavage, we suggest that the activation of the mTOR/p70S6K pathway persists for many hours after supplementation. However, Laymans group has shown that peak mTOR and insulin signaling responses occur shortly after consumption of a meal (i.e. 1-3 hrs) [30]; considering that our measures were taken 15-18 hrs after the HMβ gavage, and after an overnight fast, it is possible that we missed certain signals. Therefore, the acute (1-3 hrs post gavage) effects of HMB on translation initiation and elongation factors, as well as insulin signaling warrant further investigation.

In the current study, we investigated the intracellular signalling pathways involved in increased protein synthesis induced by HMB; however, it is important to remember that potent hormones are secreted in response to nutrients and might exert robust increases in protein synthesis and metabolism in several tissues [31-33]. In the present study, we observed that increased insulin levels may have resulted in increased mTOR levels and phosphorylation of p70S6K; however, we have no data that directly address this idea, and previous studies [30,34] do not support the idea that typical fasting insulin concentrations (above basal levels) can stimulate the mTOR/p70S6K pathway.

As discussed above, several studies [16,22,26] have been performed to determine the main mechanism of action of HMβ. Based on the results of this study, we have outlined the main mechanisms of HMβ action as being related to increases in mTOR/p70S6K pathway signalling and most likely leading to improved protein synthesis and muscle hypertrophy. However, it is important to note that protein synthesis pathways are extremely redundant, and other important proteins not evaluated in our study, such as the eukaryotic translation initiation factor 4E (eIF4E/2B), might play a role in the observed final response (i.e., muscle hypertrophy).

In accordance with this idea, hormones control anabolic/catabolic pathways that can favour (insulin, testosterone) or antagonise (glucocorticoid hormones) [35,36] anabolism in skeletal muscle. In fact, we observed low serum corticosterone levels and high testosterone/corticosterone ratios after HMβ supplementation, which could contribute to skeletal muscle hypertrophy. Likewise, Olza et al. [37] observed that in elderly patients, a protein-enriched diet was able to increase protein synthesis and reduce protein degradation. Moreover, the reduction in corticosterone and increase in insulin levels may have favoured the reduction in fasting blood glucose after HMβ supplementation. Recently, Guo et al. [38] also found improvements in glucose homeostasis after leucine supplementation.

Hepatic lipid levels were not altered, as shown in Table ​Table2.2. These results are consistent with the lack of change in serum lipid levels. Several studies [3,17] have shown that HMβ is metabolised to HMG-CoA and used for de novo synthesis of cholesterol in certain tissues, including the liver. However, this conclusion is debatable; Holecek et al. [17] showed increases in serum cholesterol levels after HMβ administration, while Nissen and Abumrad [3] showed decreases in LDL-c.

In the present study, we also demonstrated an increase in skeletal muscle weight (EDL and soleus) in the absence of changes in total body mass, fat mass or liver weight. However, is suggesting that other body measures of body fat, such as the size of different fat deposits, e.g., epididymal fat, may have changed.

As stated previously, the effects of HMβ supplementation in peripheral tissues have not been intensely investigated. In accordance with this, Pedrosa et al. [39] showed that leucine supplementation increased liver protein content. However, in this study, we thoroughly investigated HMβ's effects on proteins involved in insulin signalling, starting with the insulin receptor (IR), and showed that HMβ supplementation stimulated IR expression in the liver, likely due to mTOR activation. However, the effects of long-term HMβ supplementation on this outcome are as yet unknown.

In summary, HMβ treatment leads to skeletal muscle hypertrophy via increases in mTOR expression and decreases in serum corticosterone concentrations. In addition, HMβ supplementation increases IR expression in the liver compared to control group. Thus, our results suggest that HMβ supplementation can be used to increase muscle mass without adverse health effects.

[shobhit1978]

Effect of leucine metabolite beta-hydroxy-beta-methylbutyrate on muscle metabolism during resistance-exercise training.
Nissen S, Sharp R, Ray M, Rathmacher JA, Rice D, Fuller JC Jr, Connelly AS, Abumrad N.
Source

Iowa State University, Ames 50011, USA.
Abstract

The effects of dietary supplementation with the leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) were studied in two experiments. In study 1, subjects (n = 41) were randomized among three levels of HMB supplementation (0, 1.5 or 3.0 g HMB/day) and two protein levels (normal, 117 g/day, or high, 175 g/day) and weight lifted for 1.5 h 3 days/wk for 3 wk. In study 2, subjects (n = 28) were fed either 0 or 3.0 g HMB/day and weight lifted for 2-3 h 6 days/wk for 7 wk. In study 1, HMB significantly decreased the exercise-induced rise in muscle proteolysis as measured by urine 3-methylhistidine during the first 2 wk of exercise (linear decrease, P < 0.04). Plasma creatine phosphokinase was also decreased with HMB supplementation (week 3, linear decrease, P < 0.05). Weight lifted was increased by HMB supplementation when compared with the unsupplemented subjects during each week of the study (linear increase, P < 0.02). In study 2, fat-free mass was significantly increased in HMB-supplemented subjects compared with the unsupplemented group at 2 and 4-6 wk of the study (P < 0.05). In conclusion, supplementation with either 1.5 or 3 g HMB/day can partly prevent exercise-induced proteolysis and/or muscle damage and result in larger gains in muscle function associated with resistance training.

[shobhit1978]

Nutritional role of the leucine metabolite β-hydroxy β-methylbutyrate (HMB)☆

Steven L. Nissen
,
Naji N. Abumrad

Received 14 October 1996; accepted 11 February 1997.

Abstract
Abstract + References
PDF
References

Abstract

This review develops the hypothesis that a metabolite of leucine termed β-hydroxy β-methylbutyrate (HMB) plays a key role in animal metabolism and that in certain circumstances insufficient amounts of HMB are either consumed in the diet or produced endogenously to supply tissue needs. The origin and metabolism of HMB is reviewed including the role of HMB in cholesterol biosynthesis. HMB feeding studies in animals are reviewed, which indicate that dietary supplementation of HMB can improve immune function and health and can increase the fat content of milk in lactating animals. Seven human studies are reviewed where HMB was fed. The results of both animal and human studies indicate that dietary supplementation of HMB is safe, as evidenced by lack of physical adverse effects and a lack of effect on blood hematology and chemistry. The only consistent change in blood chemistry was a decrease in LDL cholesterol, which changed 7% (P < .01). In humans undergoing resistance training, HMB supplementation increased lean mass gains from 50 to 200%, with similar percentage increases in strength when compared with unsupplemented subjects. The effects of HMB on muscle size and function seems to result from a diminution of exercise-related muscle damage and muscle protein breakdown. A general hypothesis is proposed that HMB is metabolized to HMG-CoA in tissues such as muscle, mammary tissue, and certain immune cells and is used for de novo cholesterol synthesis. In times of stimulated growth and/or differentiation. HMG-CoA may be rate-limiting for cholesterol synthesis, which could limit cell growth or function. It is proposed that feeding HMB can provide a saturating source of cytosolic HMG-CoA for cholesterol synthesis and in turn allow for maximal cell growth and function.

[shobhit1978]

Beta-hydoxy-beta-methylbutyrate supplementation affects Walker 256 tumor-bearing rats in a time-dependent manner.
Caperuto EC, Tomatieli RV, Colquhoun A, Seelaender MC, Costa Rosa LF.
Source

Biomedical Sciences Institute, Cell Biology and Development, Lineu Prestes Av. 1524 ICB 1 Room 430, 05508-900 Sao Paulo, Sao Paulo, Brazil.
Abstract
BACKGROUND &#38; AIMS:

Cancer cachexia affects intermediary metabolism with intense and general catabolism. Walker 256 tumor is a model injected either subcutaneously (Sc) or intraperitoneally (Ip), with different metabolic features. Beta-hydroxy beta-methylbutyrate (HMbeta) is a leucine metabolite with anti-catabolic properties, the aim of this study being to investigate its effects on metabolic parameters in both tumor models.
METHODS:

Controls (subcutaneous control group (ScC) and intraperitoneal control group (IpC)) and supplemented animals (subcutaneous supplemented group (ScS) and intraperitoneal supplemented group (IpS)) showed these results.
RESULTS:

Protein Sc values were (47.8%) lower than Ip groups. Sc group fat content was (65.16%) higher than Ip groups. Liver glycogen value for Sc groups was (38.4%) higher than Ip groups. Muscle glycogen value for Sc groups were (2.75 times) higher than Ip groups. Corticosterone and insulin values were lower (44.53%) and higher (45.94%), respectively, in Sc when compared with Ip groups. Glucose and lactate values for ScS were the lowest (61.7% and 41.53%) compared to other groups. ScC glutamine value was the highest (40.8%) of all groups. Glutamate Sc values were (42.65%) lower than Ip groups. Sc groups showed greater survival time compared with Ip groups. ScS group showed 100% increase in survival time when compared with ScC.
CONCLUSIONS:

HMbeta supplementation can increase survival time and promotes metabolic changes in cancer-bearing animals, but it seems to work in a time-dependent manner.

[shobhit1978]

Nutritional supplementation of the leucine metabolite beta-hydroxy-beta-methylbutyrate (hmb) during resistance training.
Panton LB, Rathmacher JA, Baier S, Nissen S.
Source

Department of Education, East Tennessee State University, Johnson City, Tennessee 37614, USA. panton@etsu-tn.edu
Abstract

The effects of supplementation of the leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) were examined in a resistance training study. Thirty-nine men and 36 women between the ages of 20-40 y were randomized to either a placebo (P) supplemented or HMB supplemented (3.0 g HMB/d) group in two gender cohorts. All subjects trained three times per week for 4 wk. In the HMB group, plasma creatine phosphokinase levels tended to be suppressed compared to the placebo group following the 4 wk of resistance training (HMB:174. 4 +/- 26.8 to 173.5 +/- 17.0 U/L; P:155.0 +/- 20.8 to 195.2 +/- 23.5 U/L). There were no significant differences in strength gains based on prior training status or gender with HMB supplementation. The HMB group had a greater increase in upper body strength than the placebo group (HMB:7.5 +/- 0.6 kg; P:5.2 +/- 0.6 kg; P = 0.008). The HMB groups increased fat-free weight by 1.4 +/- 0.2 kg and decreased percent fat by 1.1% +/- 0.2% while the placebo groups increased fat-free weight by 0.9 +/- 0.2 kg and decreased percent fat by 0.5% +/- 0.2% (fat-free weight P = 0.08, percent fat P = 0.08, HMB compared to placebo). In summary, this is the first short-term study to investigate the roles of gender and training status on the effects of HMB supplementation on strength and body composition. This study showed, regardless of gender or training status, HMB may increase upper body strength and minimize muscle damage when combined with an exercise program.

[shobhit1978]

Creatine and beta-hydroxy-beta-methylbutyrate (HMB) additively increase lean body mass and muscle strength during a weight-training program.
Jówko E, Ostaszewski P, Jank M, Sacharuk J, Zieniewicz A, Wilczak J, Nissen S.
Source

Institute of Sport and Physical Education, Biala Podlaska, Academy of Physical Education, Warsaw, Poland.
Abstract

We investigated whether creatine (CR) and beta-hydroxy-beta-methylbutyrate (HMB) act by similar or different mechanisms to increase lean body mass (LBM) and strength in humans undergoing progressive resistance-exercise training. In this double-blind, 3-wk study, subjects (n = 40) were randomized to placebo (PL; n = 10), CR (20.0 g of CR/d for 7 d followed by 10.0 g of CR/d for 14 d; n = 11), HMB (3.0 g of HMB/d; n = 9), or CR-and-HMB (CR/HMB; n = 10) treatment groups. Over 3 wk, all subjects gained LBM, which was assessed by bioelectrical impedance analysis. The CR, HMB and CR/HMB groups gained 0.92, 0.39, and 1.54 kg of LBM, respectively, over the placebo group, with a significant effect with CR supplementation (main effect P = 0.05) and a trend with HMB supplementation (main effect P = 0.08). These effects were additive because there was no interaction between CR and HMB (CR x HMB main effect P = 0.73). Across all exercises, HMB, CR, and CR/HMB supplementation caused accumulative strength increases of 37.5, 39.1, and 51.9 kg, respectively, above the placebo group. The exercise-induced rise in serum creatine phosphokinase was markedly suppressed with HMB supplementation (main effect P = 0.01). However, CR supplementation antagonized the HMB effects on serum creatine phosphokinase (CR x HMB interactive effect P = 0.04). Urine urea nitrogen and plasma urea were not affected by CR supplementation, but both decreased with HMB supplementation (HMB effect P < 0.05), suggesting a nitrogen-sparing effect. In summary, CR and HMB can increase LBM and strength, and the effects are additive. Although not definitive, these results suggest that CR and HMB act by different mechanisms.

[shobhit1978]

Beta-hydroxy-beta-methylbutyrate supplementation reduces tumor growth and tumor cell proliferation ex vivo and prevents cachexia in Walker 256 tumor-bearing rats by modifying nuclear factor-kappaB expression.
Nunes EA, Kuczera D, Brito GA, Bonatto SJ, Yamazaki RK, Tanhoffer RA, Mund RC, Kryczyk M, Fernandes LC.
Source

Department of Physiology, Biological Science Building, Federal University of Paraná, 81531-980 Curitiba-PR, Brazil. eanunes@ufpr.br
Abstract

Cancer cachexia syndrome contributes to wasting and weight loss leading to inefficacy of anticancer therapy. In this study, the anticatabolic agent beta-hydroxy-beta-methylbutyrate (HMB) was supplemented to adult Walker 256 tumor-bearing rats during 8 weeks aiming to determine if tumor burden could be reduced. Male Wistar rats were randomly assigned to nontumor and tumor-bearing groups and fed regular chow or regular chow plus HMB supplemented (76 mg/kg body weight). Beta-hydroxy-beta-methylbutyrate supplementation induced a lower tumor weight and tumor cell proliferation ex vivo, totally prevented glycemia reduction, as well as blunted the increase in the serum lactate concentrations and also preserved glycogen stores in tumor-bearing rats. Reduction in tumor cell proliferation ex vivo was accompanied by increased nuclear factor-kappaB inhibitor-alpha content by more than 100%. In contrast, nuclear factor-kappaB p65 subunit content was suppressed by 17% with HMB supplementation. In conclusion, HMB supplementation, at a similar dose used in humans to increase muscle mass, caused antitumor and anticachectic effects, with tumor-cell nuclear factor-kappaB pathway participation, which might be a potential nutritional strategy in cancer therapy.

[shobhit1978]

Nutritional Treatment for Acquired Immunodeficiency Virus-Associated Wasting Using β-Hydroxy β-Methylbutyrate, Glutamine, and Arginine: A Randomized, Double-Blind, Placebo-Controlled Study

Robert H. Clark, MD

Nassau County Medical Center, East Meadow, New York

Getachew Feleke, MD

Nassau County Medical Center, East Meadow, New York

Mehraj Din, MD

Nassau County Medical Center, East Meadow, New York

Tabassum Yasmin, MD

Nassau County Medical Center, East Meadow, New York

Gurpreet Singh, MD

Nassau County Medical Center, East Meadow, New York

Faroque A. Khan, MB, MACP

Nassau County Medical Center, East Meadow, New York

John A. Rathmacher, PhD

Iowa State University, Ames, Iowa, jarat@iastate.edu

Abstract

Background: The current study was designed to examine whether a combination of three nutrients, consisting of β-hydroxy-β-methylbutyrate (HMB), a metabolite of leucine, L-glutamine (Gln) and L-arginine (Arg), each of which has been previously shown to slow muscle proteolysis, could synergistically alter the course of muscle wasting in patients with established acquired immunodeficiency syndrome (AIDS). Methods: Sixty-eight human immunodeficiency virus (HIV)-infected patients with a documented weight loss of at least 5% in the previous 3 months were recruited from the HIV clinic at Nassau County Medical Center. The subjects were randomly assigned in a double-blind fashion to receive either placebo containing maltodextrin or the nutrient mixture (HMB/Arg/Gln) containing 3 g HMB, 14 g L-glutamine, and 14 g L-arginine given in two divided doses daily for 8 weeks. Body weights (BW) were recorded weekly and lean body mass (LBM) and fat mass (FM) were measured by air displacement plethysmography and by a single computerized tomography (CT) slice through the thigh at 0, 4, and 8 weeks. Results: Forty-three subjects completed the 8-week protocol, (placebo, n = 21; HMB/Arg/Gln, n = 22). At 8 weeks, the subjects consuming the HMB/Arg/Gln mixture gained 3.0 ± 0.5 kg of BW while those supplemented with the placebo gained 0.37 ± 0.84 kg (p = .009). The BW gain in the HMB/Arg/Gln-treated subjects was predominantly LBM (2.55 ± 0.75 kg) compared with the placebo-supplemented subjects who lost lean mass (-0.70 ± 0.69 kg, p = .003). No significant change in FM gain was observed (0.43 ± 0.83 kg for the group receiving HMB/Arg/Gln and 1.07 ± 0.64 kg for the group receiving the placebo, p > .20). Similar percentage changes in muscle mass and fat mass were observed with CT scans. Immune status was also improved as evident by an increase in CD3 and CD8 cells and a decrease in the HIV viral load with HMB/Arg/Gln supplementation. Conclusions: The data indicate that the HMB/Arg/Gln mixture can markedly alter the course of lean tissue loss in patients with AIDS-associated wasting. (Journal of Parenteral and Enteral Nutrition 24:133-139, 2000)

[shobhit1978]

HMB supplementation: clinical and athletic performance-related effects and mechanisms of action.
Zanchi NE, Gerlinger-Romero F, Guimarães-Ferreira L, de Siqueira Filho MA, Felitti V, Lira FS, Seelaender M, Lancha AH Jr.
Source

Laboratory of Applied Nutrition and Metabolism, Physical Education and Sports School, University of Sao Paulo, São Paulo, Brazil. neloz@ig.com.br
Abstract

Amino acids such as leucine and its metabolite α-ketoisocaproate (KIC), are returning to be the focus of studies, mainly because of their anti-catabolic properties, through inhibition of muscle proteolysis and enhancement of protein synthesis. It is clear that these effects may counteract catabolic conditions, as well as enhance skeletal muscle mass and strength in athletes. Moreover, beta-hydroxy-beta-methylbutyrate (HMB) has been shown to produce an important effect in reducing muscle damage induced by mechanical stimuli of skeletal muscle. This review aims to describe the general scientific evidence of KIC and HMB supplementation clinical relevance, as well as their effects (e.g., increases in skeletal muscle mass and/or strength), associated with resistance training or other sports. Moreover, the possible mechanisms of cell signaling regulation leading to increases and/or sparing (during catabolic conditions) of skeletal muscle mass are discussed in detail based on the recent literature.

[shobhit1978]

Effects of beta-hydroxy-beta-methylbutyrate (HMB) on exercise performance and body composition across varying levels of age, sex, and training experience: A review

Gabriel J Wilson1*, Jacob M Wilson2 and Anssi H Manninen3

* Corresponding author: Gabriel J Wilson gwilson@abcbodybuilding.com

Author Affiliations

1 Division of Nutritional Sciences, University of Illinois, Urbana, Illinois, USA

2 Department of Nutrition, Food and Exercise Science, Florida State University, Tallahassee, Florida, USA

3 Manninen Nutraceuticals Oy, Oulu, Finland

For all author emails, please log on.

Nutrition & Metabolism 2008, 5:1 doi:10.1186/1743-7075-5-1

The electronic version of this article is the complete one and can be found online at:

Received: 27 June 2007
Accepted: 3 January 2008
Published: 3 January 2008

© 2008 Wilson et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract

The leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) has been extensively used as an ergogenic aid; particularly among bodybuilders and strength/power athletes, who use it to promote exercise performance and skeletal muscle hypertrophy. While numerous studies have supported the efficacy of HMB in exercise and clinical conditions, there have been a number of conflicting results. Therefore, the first purpose of this paper will be to provide an in depth and objective analysis of HMB research. Special care is taken to present critical details of each study in an attempt to both examine the effectiveness of HMB as well as explain possible reasons for conflicting results seen in the literature. Within this analysis, moderator variables such as age, training experience, various states of muscle catabolism, and optimal dosages of HMB are discussed. The validity of dependent measurements, clustering of data, and a conflict of interest bias will also be analyzed. A second purpose of this paper is to provide a comprehensive discussion on possible mechanisms, which HMB may operate through. Currently, the most readily discussed mechanism has been attributed to HMB as a precursor to the rate limiting enzyme to cholesterol synthesis HMG-coenzyme A reductase. However, an increase in research has been directed towards possible proteolytic pathways HMB may operate through. Evidence from cachectic cancer studies suggests that HMB may inhibit the ubiquitin-proteasome proteolytic pathway responsible for the specific degradation of intracellular proteins. HMB may also directly stimulate protein synthesis, through an mTOR dependent mechanism. Finally, special care has been taken to provide future research implications.

[shobhit1978]

Dietary treatment of rheumatoid cachexia with beta-hydroxy-beta-methylbutyrate, glutamine and arginine: a randomised controlled trial.
Marcora S, Lemmey A, Maddison P.
Source

School of Sport, Health and Exercise Sciences, University of Wales-Bangor, George Building, Holyhead Road, Bangor, Gwynedd LL57 2PX, UK. s.m.marcora@bangor.ac.uk
Abstract
BACKGROUND &#38; AIMS:

Rheumatoid arthritis (RA) is complicated by cytokine-driven alterations in protein and energy metabolism and consequent muscle wasting (cachexia). The aim of this randomised controlled trial was to investigate the efficacy of a mixture of beta-hydroxy-beta-methylbutyrate, glutamine and arginine (HMB/GLN/ARG) as nutritional treatment for rheumatoid cachexia.
METHODS:

Forty RA patients supplemented their diet with either HMB/GLN/ARG or a nitrogen (7.19 g/day) and calorie (180 kcal/day) balanced mixture of alanine, glutamic acid, glycine, and serine (placebo) for 12 weeks. Body composition and other outcomes were assessed at baseline and follow-up, and analysed by mixed ANOVA.
RESULTS:

Dietary supplementation with HMB/GLN/ARG was not superior to placebo in the treatment of rheumatoid cachexia (groupxtime interactions P>0.05 for all outcomes). Both amino acid mixtures significantly increased (main effect of time) fat-free mass (727+/-1186 g, P<0.01), total body protein (719+/-1703 g, P=0.02), arms (112+/-183 g, P<0.01) and legs (283+/-534 g, P<0.01) lean mass, and some measures of physical function. No significant adverse event occurred during the study, but patients in the HMB/GLN/ARG group reported fewer gastrointestinal complaints compared to placebo.
CONCLUSIONS:

Dietary supplementation with HMB/GLN/ARG is better tolerated but not more effective in reversing cachexia in RA patients compared to the mixture of other non-essential amino acids used as placebo. Further controlled studies are necessary to confirm the beneficial anabolic and functional effects of increased nitrogen intake in this population.

[shobhit1978]

Short-term beta-hydroxy-beta-methylbutyrate supplementation does not reduce symptoms of eccentric muscle damage.
Paddon-Jones D, Keech A, Jenkins D.
Source

School of Human Movement Studies at The University of Queensland, Brisbane, Australia. djpaddon@utmb.edu
Abstract
PURPOSE:

We examined the effects of short-term beta-hydroxy-beta-methylbutyrate (HMB) supplementation on symptoms of muscle damage following an acute bout of eccentric exercise.
METHODS:

Non-resistance trained subjects were randomly assigned to a HMB supplement group (HMB, 40mg/kg bodyweight/day, n = 8) or placebo group (CON, n = 9). Supplementation commenced 6 days prior to a bout of 24 maximal isokinetic eccentric contractions of the elbow flexors and continued throughout post-testing. Muscle soreness, upper arm girth, and torque measures were assessed pre-exercise, 15 min post-exercise, and 1, 2, 3, 4, 7, and 10 days post-exercise.
RESULTS:

No pre-test differences between HMB and CON groups were identified, and both performed a similar amount of eccentric work during the main eccentric exercise bout (p > .05). HMB supplementation had no effect on swelling, muscle soreness, or torque following the damaging eccentric exercise bout (p > .05).
CONCLUSION:

Compared to a placebo condition, short-term supplementation with 40mg/kg bodyweight/day of HMB had no beneficial effect on a range of symptoms associated with eccentric muscle damage. If HMB can produce an ergogenic response, a longer preexercise supplementation period may be necessary.

[shobhit1978]

Effect of beta-hydroxy-beta-methylbutyrate (HMB) on protein metabolism in whole body and in selected tissues.
Holecek M, Muthny T, Kovarik M, Sispera L.
Source

Department of Physiology and Biochemistry, Charles University, Medical Faculty, Hradec Kralove, Czech Republic. holecek@lfhk.cuni.cz
Abstract

Beta-hydroxy-beta-methylbutyrate (HMB) is a leucine metabolite with protein anabolic effect. The aim of the study was to examine the role of exogenous HMB on leucine and protein metabolism in whole body and selected tissues. Rats were administered by HMB (0.1 g/kg b.w.) or by saline. The parameters of whole-body protein metabolism were evaluated 24 h later using L-[1-14C]leucine and L-[3,4,5-3H]phenylalanine. Changes in proteasome dependent proteolysis and protein synthesis were determined according the "chymotrypsin-like" enzyme activity and labeled leucine and phenylalanine incorporation into the protein. A decrease in leucine clearance and whole-body protein turnover (i.e., a decrease in whole-body proteolysis and protein synthesis) was observed in HMB treated rats. Proteasome-dependent proteolysis decreased significantly in skeletal muscle, changes in heart, liver, jejunum, colon, kidney, and spleen were insignificant. Decrease in protein synthesis was observed in the heart, colon, kidney, and spleen, while an increase was observed in the liver. There were no significant changes in leucine oxidation. We conclude that protein anabolic effect of HMB in skeletal muscle is related to inhibition of proteolysis in proteasome. Alterations in protein synthesis in visceral tissues may affect several important functions and the metabolic status of the whole body.

[shobhit1978]

Beta-hydroxy-beta-methylbutyrate (HMB) stimulates myogenic cell proliferation, differentiation and survival via the MAPK/ERK and PI3K/Akt pathways.
Kornasio R, Riederer I, Butler-Browne G, Mouly V, Uni Z, Halevy O.
Source

Department of Animal Sciences, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot 76100, Israel.
Abstract

Beta-hydroxy-beta-methylbutyrate (HMB), a leucine catabolite, has been shown to prevent exercise-induced protein degradation and muscle damage. We hypothesized that HMB would directly regulate muscle-cell proliferation and differentiation and would attenuate apoptosis, the latter presumably underlying satellite-cell depletion during muscle degradation or atrophy. Adding various concentrations of HMB to serum-starved myoblasts induced cell proliferation and MyoD expression as well as the phosphorylation of MAPK/ERK. HMB induced differentiation-specific markers, increased IGF-I mRNA levels and accelerated cell fusion. Its inhibition of serum-starvation- or staurosporine-induced apoptosis was reflected by less apoptotic cells, reduced BAX expression and increased levels of Bcl-2 and Bcl-X. Annexin V staining and flow cytometry analysis showed reduced staurosporine-induced apoptosis in human myoblasts in response to HMB. HMB enhanced the association of the p85 subunit of PI3K with tyrosine-phosphorylated proteins. HMB elevated Akt phosphorylation on Thr308 and Ser473 and this was inhibited by Wortmannin, suggesting that HMB acts via Class I PI3K. Blocking of the PI3K/Akt pathway with specific inhibitors revealed its requirement in mediating the promotive effects of HMB on muscle cell differentiation and fusion. These direct effects of HMB on myoblast differentiation and survival resembling those of IGF-I, at least in culture, suggest its positive influence in preventing muscle wasting.

[shobhit1978]

The leucine metabolite 3-hydroxy-3-methylbutyrate (HMB) modifies protein turnover in muscles of laboratory rats and domestic chickens in vitro

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This study was conducted to assess the in vitro effects of leucine and 3-hydroxy-3-methylbutyrate (HMB) on protein synthesis and degradation in isolated rat and chick muscles. Isolated muscles — extensor digitorum longus (EDL) and soleus (S) in rats and EDL and tibialis anterior (TA) in chicks — were taken out intact and incubated in Krebs—Henseleit buffer with [14C]phenylalanine. Protein synthesis was then determined by measuring [14C]phenylalanine incorporation into protein and protein breakdown was estimated by net release of tyrosine from muscle proteins. In all muscles investigated leucine stimulated protein synthesis (average 20%; p < 0.05 versus control) but only slightly reduced proteolysis (average 8%, NS). In contrast, HMB had no significant effect on protein synthesis but consistently decreased protein degradation in the range from −29% (p < 0.01 versus control) in rat extensor digitorus longus to −5% (NS) in rat soleus muscles. HMB appeared to suppress protein degradation more in white muscle fibres than in red muscle fibres (at least in the rat). These data support observations in humans indicating that HMB decreases muscle proteolysis. It is suggested that metabolism of leucine to HMB could be responsible for the reported suppressive effects of leucine on protein breakdown.

[shobhit1978]

Attenuation of depression of muscle protein synthesis induced by lipopolysaccharide, tumor necrosis factor, and angiotensin II by β-hydroxy-β-methylbutyrate

Helen L. Eley,
Steven T. Russell, and
Michael J. Tisdale

+ Author Affiliations

Nutritional Biomedicine, School of Life and Health Sciences, Aston University, Birmingham, United Kingdom

Address for reprint requests and other correspondence: M. J. Tisdale, Nutritional Biomedicine, School of Life and Health Sciences, Aston Univ., Birmingham, B4 7ET, UK (e-mail: m.j.tisdale@aston.ac.uk)

Submitted 7 July 2008.
Accepted 8 October 2008.

Abstract

β-Hydroxy-β-methylbutyrate (HMB; 50 μM) has been shown to attenuate the depression in protein synthesis in murine myotubes in response to lipopolysaccharide (LPS), tumor necrosis factor-α (TNF-α) with or without interferon-γ (IFN-γ), and angiotensin II (ANG II). The mechanism for the depression of protein synthesis by all three agents was the same and was attributed to activation of double-stranded RNA-dependent protein kinase (PKR) with the subsequent phosphorylation of eukaryotic initiation factor 2 (eIF2) on the α-subunit as well as increased phosphorylation of the elongation factor (eEF2). Myotubes expressing a catalytically inactive PKR variant, PKRΔ6, showed no depression of protein synthesis in response to either LPS or TNF-α, confirming the importance of PKR in this process. There was no effect of any of the agents on phosphorylation of mammalian target of rapamycin (mTOR) or initiation factor 4E-binding protein (4E-BP1), and thus no change in the amount of eIF4E bound to 4E-BP1 or the concentration of the active eIF4E·eIF4G complex. HMB attenuated phosphorylation of eEF2, possibly by increasing phosphorylation of mTOR, and also attenuated phosphorylation of eIF2α by preventing activation of PKR. These results suggest that HMB may be effective in attenuating muscle atrophy in a range of catabolic conditions.

[shobhit1978]

Mechanism of attenuation of muscle protein degradation induced by tumor necrosis factor-α and angiotensin II by β-hydroxy-β-methylbutyrate

Helen L. Eley,
Steven T. Russell, and
Michael J. Tisdale

+ Author Affiliations

Nutritional Biomedicine, School of Life and Health Sciences, Aston University, Birmingham, United Kingdom

Address for reprint requests and other correspondence: M. J. Tisdale, Nutritional Biomedicine, School of Life and Health Sciences, Aston Univ., Birmingham, B4 7ET, UK (e-mail: m.j.tisdale@aston.ac.uk)

Submitted 7 July 2008.
Accepted 6 October 2008.

Abstract

Both tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ) and angiotensin II (ANG II) induced an increase in total protein degradation in murine myotubes, which was completely attenuated by treatment with β-hydroxy-β-methylbutyrate (HMB; 50 μM). There was an increase in formation of reactive oxygen species (ROS) within 30 min, as well as an increase in the activity of both caspase-3 and -8, and both effects were attenuated by HMB. Moreover, inhibitors of caspase-3 and -8 completely attenuated both ROS formation and total protein degradation induced by TNF-α/IFN-γ and ANG II. There was an increased autophosphorylation of double-stranded RNA-dependent protein kinase (PKR), which was attenuated by the specific caspase-3 and -8 inhibitors. Neither ROS formation or protein degradation occurred in myotubes expressing a catalytically inactive PKR variant, PKRΔ6, in response to TNF-α/IFN-γ, compared with myotubes expressing wild-type PKR, although there was still activation of caspase-3 and -8. HMB also attenuated activation of PKR, suggesting that it was important in protein degradation. Formation of ROS was attenuated by rotenone, an inhibitor of the mitochondrial electron transport chain, nitro-l-arginine methyl ester, an inhibitor of nitric oxide synthase, and SB 203580, a specific inhibitor of p38 mitogen-activated protein kinase (p38 MAPK), which also attenuated total protein degradation. Activation of p38 MAPK by PKR provides the link to ROS formation. These results suggest that TNF-α/IFN-γ and ANG II induce muscle protein degradation by a common signaling pathway, which is attenuated by HMB, and that this involves the initial activation of caspase-3 and -8, followed by autophosphorylation and activation of PKR, which then leads to increased ROS formation via activation of p38 MAPK. Increased ROS formation is known to induce protein degradation through the ubiquitin-proteasome pathway.

[shobhit1978]

Attenuation of Proteasome-Induced Proteolysis in Skeletal Muscle by β-Hydroxy-β-Methylbutyrate in Cancer-Induced Muscle Loss

Helen J. Smith1,
Pradip Mukerji2, and
Michael J. Tisdale1

+ Author Affiliations

1Pharmaceutical Sciences Research Institute, Aston University, Birmingham, United Kingdom and 2Ross Products Division, Abbott Laboratories, Columbus, Ohio, USA

Requests for reprints:
Michael J. Tisdale, Pharmaceutical Sciences Research Institute, Aston University, Birmingham, B4 7ET, United Kingdom. Phone: 44-121-359-3611; Fax: 44-121-333-3172; E-mail: m.j.tisdale@aston.ac.uk

Abstract

Loss of skeletal muscle is an important determinant of survival in patients with cancer-induced weight loss. The effect of the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) on the reduction of body weight loss and protein degradation in the MAC16 model of cancer-induced weight loss has been compared with that of eicosapentaenoic acid (EPA), a recognized inhibitor of protein degradation. HMB was found to attenuate the development of weight loss at a dose greater than 0.125 g/kg accompanied by a small reduction in tumor growth rate. When EPA was used at a suboptimal dose level (0.6 g/kg) the combination with HMB seemed to enhance the anticachectic effect. Both treatments caused an increase in the wet weight of soleus muscle and a reduction in protein degradation, although there did not seem to be a synergistic effect of the combination. Proteasome activity, determined by the “chymotrypsin-like” enzyme activity, was attenuated by both HMB and EPA. Protein expression of the 20S α or β subunits was reduced by at least 50%, as were the ATPase subunits MSS1 and p42 of the 19S proteasome regulatory subunit. This was accompanied by a reduction in the expression of E214k ubiquitin-conjugating enzyme. The combination of EPA and HMB was at least as effective or more effective than either treatment alone. Attenuation of proteasome expression was reflected as a reduction in protein degradation in gastrocnemius muscle of cachectic mice treated with HMB. In addition, HMB produced a significant stimulation of protein synthesis in skeletal muscle. These results suggest that HMB preserves lean body mass and attenuates protein degradation through down-regulation of the increased expression of key regulatory components of the ubiquitin-proteasome proteolytic pathway, together with stimulation of protein synthesis.

[shobhit1978]

Mechanism of the Attenuation of Proteolysis-Inducing Factor Stimulated Protein Degradation in Muscle by β-Hydroxy-β-Methylbutyrate

Helen J. Smith,
Stacey M. Wyke, and
Michael J. Tisdale

+ Author Affiliations

Pharmaceutical Sciences Research Institute, Aston University, Birmingham, United Kingdom

Abstract

The leucine metabolite β-hydroxy-β-methylbutyrate (HMB) prevents muscle protein degradation in cancer-induced weight loss through attenuation of the ubiquitin-proteasome proteolytic pathway. To investigate the mechanism of this effect, the action of HMB on protein breakdown and intracellular signaling leading to increased proteasome expression by the tumor factor proteolysis-inducing factor (PIF) has been studied in vitro using murine myotubes as a surrogate model of skeletal muscle. A comparison has been made of the effects of HMB and those of eicosapentaenoic acid (EPA), a known inhibitor of PIF signaling. At a concentration of 50 μmol/L, EPA and HMB completely attenuated PIF-induced protein degradation and induction of the ubiquitin-proteasome proteolytic pathway, as determined by the “chymotrypsin-like” enzyme activity, as well as protein expression of 20S proteasome α- and β-subunits and subunit p42 of the 19S regulator. The primary event in PIF-induced protein degradation is thought to be release of arachidonic acid from membrane phospholipids, and this process was attenuated by EPA, but not HMB, suggesting that HMB might act at another step in the PIF signaling pathway. EPA and HMB at a concentration of 50 μmol/L attenuated PIF-induced activation of protein kinase C and the subsequent degradation of inhibitor κBα and nuclear accumulation of nuclear factor κB. EPA and HMB also attenuated phosphorylation of p42/44 mitogen-activated protein kinase by PIF, thought to be important in PIF-induced proteasome expression. These results suggest that HMB attenuates PIF-induced activation and increased gene expression of the ubiquitin-proteasome proteolytic pathway, reducing protein degradation.

[shobhit1978]

Year-long Changes in Protein Metabolism in Elderly Men and Women Supplemented With a Nutrition Cocktail of β-Hydroxy-β-methylbutyrate (HMB), L-Arginine, and L-Lysine

Shawn Baier, MS1
Darcy Johannsen, PhD1
Naji Abumrad, MD, FACS2
John A. Rathmacher, PhD3,4
Steven Nissen, DVM, PhD3,4
Paul Flakoll, PhD1

From the 1Department of Food Science and Human Nutrition, Iowa State University, Ames; 2Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee;3 Department of Animal Science, Iowa State University, Ames, IA; and 4Metabolic Technologies, Iowa State University Research Park, Ames, IA.

Address correspondence to: Steven Nissen, DVM, PhD, Department of Animal Science, 313 Kildee Hall, Iowa State University, Ames, IA 50011; e-mail: nissen@iastate.edu.

Abstract

Background: A major contributing factor to the loss of mobility in elderly people is the gradual and continuous loss of lean body mass. Objectives: To determine whether supplementation of an amino acid cocktail daily for 1 year could improve the age-associated changes in protein turnover and lean body mass in elderly people. Design: Elderly (76± 1.6 years) women (n = 39) and men (n = 38) were recruited for a double-blinded controlled study. Study participants were randomly assigned to either an isonitrogenous control-supplement (n = 37) or a treatment-supplement (HMB/Arg/Lys) consisting of β-hydroxy-β-methylbutyrate, L-arginine, and L-lysine (n = 40) for the 1-year study. Lean tissue mass was measured using both bioelectrical-impedance analysis (BIA) and dual energy x-ray absorptiometry (DXA). Rates of whole-body protein turnover were estimated using primed/intermittent oral doses of 15N-glycine. Results: In subjects taking the HMB/Arg/Lys supplement, lean tissue increased over the year of study while in the control group, lean tissue did not change. Compared with control, HMB/Arg/Lys increased body cell mass (BIA) by 1.6% (P = .002) and lean mass (DXA) by 1.2% (P = .05). The rates of protein turnover were significantly increased 8% and 12% in the HMB/Arg/Lys-supplemented group while rates of protein turnover decreased 11% and 9% in the control-supplemented subjects (P < .01), at 3 and 12 months, respectively. Conclusions: Consumption of a simple amino acid-related cocktail increased protein turnover and lean tissue in elderly individuals in a year-long study.

[shobhit1978]

β-Hydroxy-β-Methylbutyrate (HMB) Supplementation in Humans Is Safe and May Decrease Cardiovascular Risk Factors

S. Nissen*,1,
R. L. Sharp*,
L. Panton*,
M. Vukovich†,
S. Trappe‡, and
J. C. Fuller Jr.**

+ Author Affiliations

*Iowa State University, Ames, IA,
†Wichita State University, Wichita, KS,
‡Ball State University, Muncie, IN and
**Metabolic Technologies Incorporated, Iowa State University Research Park, Ames, IA

↵1To whom correspondence and reprint requests should be addressed.

Abstract

The leucine metabolite, β-hydroxy-β-methylbutyrate (HMB) enhances the effects of exercise on muscle size and strength. Although several reports in animals and humans indicate that HMB is safe, quantitative safety data in humans have not been reported definitively. The objective of this work was to summarize safety data collected in nine studies in which humans were fed 3 g HMB/d. The studies were from 3 to 8 wk in duration, included both males and females, young and old, exercising or nonexercising. Organ and tissue function was assessed by blood chemistry and hematology; subtle effects on emotional perception were measured with an emotional profile test (Circumplex), and tolerance of HMB was assessed with a battery of 32 health-related questions. HMB did not adversely affect any surrogate marker of tissue health and function. The Circumplex emotion profile indicated that HMB significantly decreased (improved) one indicator of negative mood (Unactivated Unpleasant Affect category, P < 0.05). No untoward effects of HMB were indicated. Compared with the placebo, HMB supplementation resulted in a net decrease in total cholesterol (5.8%, P < 0.03), a decrease in LDL cholesterol (7.3%, P < 0.01) and a decrease in systolic blood pressure (4.4 mm Hg, P < 0.05). These effects of HMB on surrogate markers of cardiovascular health could result in a decrease in the risk of heart attack and stroke. In conclusion, the objective data collected across nine experiments indicate that HMB can be taken safely as an ergogenic aid for exercise and that objective measures of health and perception of well-being are generally enhanced.

[Right_Hook]

There is a new Tampa study coming (may be published already) that found hmb to be effective in weight trainees during periods of over training. 3grams per day.

[thefleshlight]

Is this 1990 again? Thought this shyt was proven to be junk? Maybe previous uses had under-dosed it?